Our study constructed and internally validated a simple‐to‐use integer risk score to predict future adverse events from a large international database of patients with hypertension and chronic stable CAD. This allowed us to stratify patients into low‐, intermediate‐, and high‐risk categories. Adverse outcomes were primarily attributable to deaths. Strength of the current analysis is that all of the predictors are readily available during a routine clinic visit. The risk score had good discriminative ability in determining which patients would suffer from an adverse event and provided similar predictive accuracy among different study eligibility criteria (ie, prior myocardial infarction versus only classic angina pectoris). Such information might be useful to select high‐risk patients for closer surveillance, more aggressive risk factor modification, and performance of diagnostic/therapeutic procedures, while being more conservative in low‐risk patients; however, these concepts would need to be prospectively tested. Model performance was slightly improved when comparing a model with nonmodifiable factors (C‐statistic=0.74) to models with modifiable factors (C‐statistic=0.75). This could signal the importance of weight, heart rate, and BP control among these patients.
We analyzed patients who had at least 1 postbaseline visit, and preferentially used the 6‐month visit when titration of antihypertensive medications was mostly complete. Accordingly, these results are generalizable to ambulatory patients with chronic stable CAD who are on a stable antihypertensive regimen. We decided to perform a landmark analysis for several reasons. The mean BP in INVEST was significantly reduced after study medications were initiated. This mirrors clinical practice where patients with hypertension will undergo a dedicated attempt by their practitioner to reach target BP through titration of antihypertensive medications. In lieu of mean BP which would not be readily available in clinical practice, we used a carefully measured value during 1 office visit. This correlated well with mean BP and had good or very good specificity. Patients who have a one‐time BP value within the referent range (110 to 139 mm Hg), but close to the lower/upper threshold may need additional BP readings or even ambulatory BP monitoring to accurately classify them.
Most of the predictors in this risk score have been well documented to increase the hazard for adverse events: advanced age,22,26
congestive heart failure,22,27
chronic kidney disease,26,28,30–31
and peripheral arterial disease.13,32
However, the aggregated effect of multiple risk factors among chronic stable CAD patient is less well known.26,33
Accumulating evidence is challenging the paradigm that very low BP is superior to a less stringent target for high‐risk patients. The ACCORD BP (Action to Control Cardiovascular Risk in Diabetes—Blood–Pressure‐lowering arm) trial randomized diabetic patients to a goal systolic BP <120 mm Hg (mean 119 mm Hg) compared with a goal <140 mm Hg (134 mm Hg).34
At 4.7 years of follow‐up, cardiovascular outcomes were similar in the 2 groups. An observational study conducted among diabetic patients with hypertension and stable CAD, documented similar outcomes with an achieved systolic BP <130 mm Hg compared with 130 to <140 mm Hg.16
More concerning was the group of patients who achieved a systolic BP <110 mm Hg in which case all‐cause mortality was increased. Lastly, a post‐hoc analysis from an acute coronary syndrome trial in which half of the patients had hypertension, documented increased adverse events among the group with mean systolic BP <110 mm Hg.15
Writing committees might need to consider an optimal BP range, rather than advocating a “lower is better” approach. Current secondary prevention guidelines recommend treating BP to a target <140/90 mm Hg or even lower among patients with CAD.18,35
In otherwise healthy individuals (ie, no end‐organ disease), obesity significantly shortens one's lifespan.36
Above a BMI of 25 kg/m2
, every 5 kg/m2
increase in BMI is associated with a 30% increase in mortality.36
However, once CAD (or other end‐organ disease) is established, the association between obesity and adverse outcomes becomes complex.37
This obesity paradox has been well‐described and is supported by the current study.21–23
The mechanism for this paradox is unknown; however, central obesity (ie, waist‐to‐hip ratio or waist circumference) appears to better predict adverse outcomes than BMI.38–39
Unfortunately, measurements of central obesity were not obtained in INVEST.
Patients enrolled in a clinical study can be highly motivated and might differ from the general population with CAD. Another limitation, which is due to the study period, is that study participants may not represent contemporary practice. For example, drug‐eluting stents were not used during percutaneous coronary intervention and lipid lowering therapy mostly predated the use of high‐dose statin therapy.40
Aspirin use was expected to reduce adverse outcomes22,33,41
; however, this was not the case in our analysis. Studies support the notion that CAD patients treated with aspirin are higher‐risk than CAD patients not treated with aspirin, thus resulting in confounding by indication.42
Chronic kidney disease, hyperlipidemia, and heart failure were based on physician diagnosis and patient medical records. Had serum creatinine, estimated glomerular filtration rate, lipid profile, and left ventricular ejection fraction been available, the prevalence of these conditions might have been expanded, which could have altered the risk model. Lastly, there were relatively few adverse events attributable to nonfatal myocardial infarction or stroke. Although the reason for this is unknown, the ACCORD trial similarly had a low frequency of these events despite enrolling high‐risk diabetic patients.43